aRetrovirology Research Laboratory, Pacific Biomedical Research Center, University of Hawaii, HI; ^bNational Institute of Hygiene & Epidemiology, Hanoi; and ^cPreventive Medicine Center, An Giang, Vietnam

Objective: The aim of this study was to identify molecular markers or "signature sequences" for mapping the spread of HIV-1 in Vietnam and in neighboring Southeast Asian countries. Materials and Methods: We conducted a cross-sectional study of plasma samples collected from 125 HIV-1-infected IDU (43 from the North and 82 from the South) and 71 virus-infected CSW from the South during the five-year period, 1995 to 1999. A 293-bp region, spanning the principal neutralizing domain (V3 loop) of the gp120-encoding HIV-1 env gene, was amplified from RNA extracted from plasma of individuals in the North (Hanoi, Hai Phong, Lang Son, and Quang Ninh) and the South (Ho Chi Minh City, An Giang, Can Tho, Nha Trang Khanh Hoa, Kien Giang, and Da Nang). HIV-1 nucleotide sequences from Vietnam were aligned and compared with 128 Thai, 26 Cambodian and 14 Chinese HIV-1 subtype E sequences. Genetic distances, net charge in the V3 loop, and the distribution of the specific substitutions were ascertained for all sequences. Nucleotide sequences were analyzed with respect to risk factor and geographical area. Results and Conclusions: Sequence and phylogenetic analyses of the 196 Vietnam HIV-1 strains confirmed that subtype E was the predominant genetic subtype of HIV-1 among CSW and IDU in Vietnam (subtype E, 98.5% vs. subtype B, 1.5%). Analysis of the interstrain env gene sequence diversity suggested that HIV-1 initially gained entry in CSW in southern Vietnam. Phylogenetic clustering of the southern Vietnam HIV-1 strains with virus strains from Cambodia was consistent with circular migration of virus-infected CSW. Cross-border travel of virus-infected CSW and their clients will continue to play an important role in the dissemination of HIV-1 in Southeast Asia. Unique substitutions at position 7273, 7155 and 7250 in the HIV-1 env gene among southern Vietnam IDU and CSW suggested independent introduction and spread of HIV-1 among these high-risk groups. The frequent occurrence of an amino acid-altering (isoleucine to methionine) substitution in the consensus octapeptide motif of the V3 loop and a downstream deletion in the C3 region as well as the valine substitution may serve as a useful genetic marker for mapping the spread of subtype E strains in southeast Asia. Unique and identical amino acid substitutions in the env gene of HIV-1 strains from IDU in northern Vietnam and southern China suggested cross-border travel of virus-infected IDU and further strengthens the hypothesis of HIV-1 spread via drug trafficking from Myanmar/Laos to northern Vietnam and into southern China. Significantly higher median nucleotide sequence diversity and net charge between the syncytium-inducing (SI) and nonsyncytium-inducing (NSI) virus strains suggested that molecular genetic criteria for segregation of SI and NSI viruses may be a useful cost-effective tool for predicting virus phenotype. Collectively, the molecular microepidemiology of HIV-1 infection in Vietnam is consistent with a founder effect. [Supported by USPHS grant G12AI/RR03061 from the RCMI Program, NCRR, NIH]